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1.
Support Care Cancer ; 31(8): 503, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37526784

RESUMO

BACKGROUND: There is no information on whether vulnerable older patients with cancer consider basic activities of daily living (BADL) and instrumental activities of daily living (IADL) important outcomes. Our survey aimed to investigate the priority of BADL and IADL in outcomes among vulnerable older patients with cancer. METHODS: This was a single-center survey in a Japanese cancer center. Eligible patients were ≥ 65 years of age and were prescribed in-hospital rehabilitation while under cancer treatment. Using original self-administered ranking questionnaires, patients were asked to rank outcomes and subdomain of BADL and IADL. High-priority domains were defined as the highest, second-highest, and third-highest priority domains in individuals. RESULTS: A total of 169 patients were analyzed. The mean age was 74.0 years (standard deviation, 5.1 years) and the number of males was 107 (63%). The order of ranking of high-priority outcomes was BADL and IADL (n = 155), cognitive function (n = 91), mental function (n = 82), nutrition (n = 61), social function (n = 51), comorbidity (n = 39), and life span (n = 28). The top three high-priority independence subdomains of BADL and IADL were toilet use (n = 140), feeding (n = 134), and mobility (n = 69) among the BADL and shopping (n = 93), food preparation (n = 88), and ability to handle finances (n = 85) among the IADL. CONCLUSIONS: BADL and IADL can be considered the most important health outcomes in clinical trials and in practice among older patients with cancer and physical vulnerabilities.


Assuntos
Atividades Cotidianas , Neoplasias , Masculino , Humanos , Idoso , Estudos Transversais , Comorbidade , Inquéritos e Questionários
2.
BMC Public Health ; 22(1): 1815, 2022 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-36153514

RESUMO

BACKGROUND: Accumulating social capital in urban areas is essential to improve community health. Previous studies suggested that intergenerational contact may be effective for enhancing social capital. However, no study has examined the effect of intergenerational contact on social capital through a population-based evaluation. This study aimed to investigate the effects of a community-based intervention to increase the frequency of intergenerational contact on social capital among adults aged 25-84 years. METHODS: This study used a non-randomized controlled trial design to conduct a community-based intervention (from March 2016 to March 2019). The study area was Tama ward, Kawasaki city, Kanagawa, Japan. The area comprises five districts; one district was assigned as the intervention group and the other four districts as the control group. We provided the intervention to residents in the intervention group. The intervention comprised three phases: Phase 1 was the preparation term (organizing the project committee); Phase 2 was the implementation term (trained volunteer staff members, conducted the intergenerational greeting campaign, and held intergenerational contact events); and Phase 3 was the transition term (surrendering the lead role of the project to the city hall field workers). In the control group, field workers provided public health services as usual. We conducted mail surveys in September 2016 and November 2018 to assess the effects of the intervention on social capital during Phase 2. Eligible participants were randomly selected from community-dwelling adults aged 25-84 years according to age (10,620 control group individuals and 4479 intervention group individuals). We evaluated social trust, norm of reciprocity, and social support as outcome variables. RESULTS: In total, 2518 participants completed both surveys and were analyzed (control group: 1727; intervention group: 791). We found that social trust (coefficient = 0.065; 95% confidence interval [CI]: 0.006, 0.125) and norm of reciprocity (coefficient = 0.084; 95% CI: 0.020, 0.149) positively changed in the intervention group compared with the control group. CONCLUSIONS: This community-based intervention may contribute to sustaining and improving social capital among community-dwelling adults. TRIAL REGISTRATION: UMIN000046769 (UMIN-CTR); first registered on January 28, 2022 (retrospectively registered).


Assuntos
Capital Social , Adulto , Humanos , Vida Independente , Apoio Social , Inquéritos e Questionários , Confiança
3.
J Obstet Gynaecol Res ; 48(10): 2647-2651, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35799348

RESUMO

Solitary fibrous tumors (SFTs) are rare mesenchymal cell-derived tumors that can cause substantial bleeding during surgery due to hyper-vascularization. We report a case of a large retroperitoneal SFT resected completely using an intra-aortic balloon. A 71-year-old female with a history of type 2 diabetes mellitus presented with a tumor that was diagnosed as an insulin-like growth factor-II-producing benign SFT using computed tomography-guided biopsy. The tumor had grown from 6 to 20 cm in diameter within 4 years, with concurrent and severe hypoglycemia. Preoperative computed tomography findings showed substantial blood flow toward the tumor. The retroperitoneal tumor was observed to be widely attached. Substantial hemorrhaging during tumor resection was observed despite vascular embolism. We inflated the intra-aortic balloon for 45 min and resected the tumor completely. In conclusion, large SFT resection requires preoperative tumor blood flow evaluation and preparation of both a vascular embolism and an intra-aortic balloon.


Assuntos
Diabetes Mellitus Tipo 2 , Tumores Fibrosos Solitários , Idoso , Feminino , Humanos , Cuidados Pré-Operatórios , Espaço Retroperitoneal/patologia , Tumores Fibrosos Solitários/diagnóstico por imagem , Tumores Fibrosos Solitários/cirurgia , Tomografia Computadorizada por Raios X
4.
Plant Cell Physiol ; 61(9): 1537-1547, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32433767

RESUMO

Although cyanobacteria do not possess wax ester synthase/acyl-CoA:diacylglycerol acyltransferase (WS/DGAT), the bacterial enzyme for triacylglycerol (TAG) production, there have been several studies reporting the accumulation of TAG-like compounds in cyanobacteria. In this study, we aimed to evaluate TAG productivity of the ΔrecJ::atfA strain of Synechocystis sp. PCC 6803 generated by inserting atfA encoding WS/DGAT from Acinetobacter baylyi ADP1 into recJ (sll1354), together with the wild type (WT) and the gene-disrupted strain of slr2103 having homology with eukaryotic DGAT2 gene family (Δ2103). Thin-layer chromatography (TLC) of neutral lipids or isolation of the neutral lipid-enriched fraction followed by gas chromatography or liquid chromatography-tandem mass spectrometry was employed for analyses. The ΔrecJ::atfA strain accumulated 0.508 nmol ml-1OD730-1 of TAG after a week of incubation at 100 µmol photons m-2 s-1. The saturated fatty acids C16:0 and C18:0 accounted for about 50% and 20% of the TAG fatty acids, respectively, suggesting that de novo-synthesized fatty acids were preferentially incorporated into TAG molecules. When the neutral lipid profile of the lipid extracts was examined by TLC, a spot located in a slightly lower position compared with the TAG standard was detected in WT but not in the Δ2103 strain. TAG accumulation levels of both strains was only 0.01-0.03 nmol ml-1OD730-1, but the fatty acid composition was substantially different from that of the background. These results suggest that trace amounts of TAG can be produced in Synechocystis cells by enzymes other than Slr2103, and major constituents of the TAG-like spot are unknown lipid species produced by Slr2103.


Assuntos
Acinetobacter/metabolismo , Diacilglicerol O-Aciltransferase/metabolismo , Synechocystis/metabolismo , Triglicerídeos/biossíntese , Acinetobacter/enzimologia , Acinetobacter/genética , Cromatografia Gasosa , Cromatografia em Camada Fina , Diacilglicerol O-Aciltransferase/genética , Cromatografia Gasosa-Espectrometria de Massas , Lipídeos/biossíntese , Organismos Geneticamente Modificados
5.
Nihon Koshu Eisei Zasshi ; 67(7): 452-460, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32741876

RESUMO

Objectives Many local governments and elementary and junior high schools in Japan have conducted a "greeting campaign". This has been done in order to activate communication among local residents, and to instill public spirit and sociability in students' minds. However, few studies have explored the significance of greeting campaigns. The present study investigates greeting in neighborhoods and its relationship with students' spontaneous greeting behavior. The study also seeks to understand the quantity of greeting in daily life and its association with a student's community attachment and helping behavior.Methods A self-completion questionnaire survey was conducted with 1,346 students studying in the fourth and higher grades at elementary schools, and 1,357 students in the first and second grade at junior high schools. There were 2,692 valid respondents. We performed the following analyses using the data of elementary school students and junior high school students separately. A partial correlation analysis was conducted wherein gender and grade were introduced as control variables. This analysis tested the correlation between the frequency of being greeted by surrounding people and the frequency of greeting by students, of their own accord. A path analysis that tested the relationship between students' greeting behavior, their attachment to residential areas, and helping behavior was also conducted.Results The results of the partial correlation analysis revealed that there was a positive correlation between the frequency of being greeted by surrounding people and the frequency of greeting by students, of their own accord, regardless of gender and grade. Moreover, the results of the path analysis revealed that the frequency of being greeted was positively associated with community attachment and that the frequency of students' spontaneous greeting behavior was positively associated not only with community attachment but also with helping behavior. The goodness of model fit was high for both the data of elementary school students as well as the data of junior high school students.Conclusion We found that exchanging greetings with surrounding people in daily life enhanced students' attachment to the community. In particular, we showed that students' spontaneous greeting behavior led to their helping behavior, which supports the significance of recommending greeting at home, school, or in the local community. Since there was a correlation between the frequency of being greeted and the frequency of greeting willingly, we consider that actions of surrounding adults become important to help students acquire spontaneous greeting behavior.


Assuntos
Comportamento do Adolescente , Comportamento Infantil , Comportamento de Ajuda , Apego ao Objeto , Características de Residência , Instituições Acadêmicas , Estudantes/psicologia , Adolescente , Criança , Aconselhamento , Humanos , Japão , Inquéritos e Questionários
6.
J Neurochem ; 145(1): 19-33, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29222951

RESUMO

Neuronal intrinsic homeostatic scaling-down of excitatory synapse has been implicated in epilepsy pathogenesis to prevent the neuronal circuits from hyperexcitability. Recent findings suggest a role for neuronal PAS domain protein 4 (Npas4), an activity-dependent neuron-specific transcription factor in epileptogenesis, however, the underlying mechanism by which Npas4 regulates epilepsy remains unclear. We herein propose that limbic seizure activity up-regulates Npas4-homer1a signaling in the hippocampus, thereby contributing to epileptogenesis in mice. The expression level of Npas4mRNA was significantly increased after the pentylenetetrazol (PTZ) treatment. Npas4KO mice developed kindling more rapidly than their wild-type littermates. The expression of Homer1a in the hippocampus increased after seizure activity. Npas4 increased Homer1a promoter activity in COS7 cells. The PTZ-stimulated induction of Homer1a was attenuated in the hippocampus of Npas4KO mice. The combination of fluorescence in situ hybridization and immunohistochemical analyses revealed that Homer1amRNA co-localized with the Npas4 protein after the convulsive seizure response. PTZ reduced excitatory synaptic transmission at the associational/commissural fibers-CA3 synapses through the Npas4-mediated down-regulation of postsynaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors in hippocampal CA3 neurons. The adeno-associated virus (AAV)-mediated expression of Homer1a resulted in lower α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptor GluA1 subunit levels in the hippocampal plasma membrane fraction than in that from AAV-EGFP-transfected Npas4KO mice. The development of kindling was more strongly suppressed in AAV-Homer1a-microinjected Npas4KO mice than in AAV-EGFP-microinjected Npas4KO mice. These results indicate that Npas4 functions as a molecular switch to initiate homeostatic scaling and the targeting of Npas4-Homer1a signaling may provide new approaches for the treatment of epilepsy.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Epilepsia/metabolismo , Proteínas de Arcabouço Homer/metabolismo , Neurônios/metabolismo , Animais , Convulsivantes/toxicidade , Epilepsia/induzido quimicamente , Homeostase/fisiologia , Excitação Neurológica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pentilenotetrazol/toxicidade , Regulação para Cima
7.
Langmuir ; 34(4): 1666-1672, 2018 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-29323910

RESUMO

Coordination polymer (CP) nanoparticles (NPs) formed by a self-assembly of organic ligands and metal ions are one of the attractive materials for molecular capture and deliver/release in aqueous media. Control of particle size and prevention of aggregation among CP NPs are important factors for improving their adsorption capability in water. We demonstrate here the potential of a liposome incorporating an antibiotic ion channel as a vessel for synthesizing Prussian blue (PB) NPs, being a typical CP. In the formation of PB NPs within liposomes, the influx rate of Fe2+ ions into liposome encapsulated [Fe(CN)6]3- through channels was fundamental for the change of NPs' sizes. The optimized PB NP-liposome composite showed higher adsorption capacity of Cs+ ions than that of aggregated PB NPs that are prepared without liposome in aqueous media.


Assuntos
Césio/química , Ferrocianetos/química , Canais Iônicos/química , Lipossomos/química , Lipossomos/síntese química , Nanopartículas/química , Adsorção , Polímeros/química
8.
Nihon Koshu Eisei Zasshi ; 65(12): 719-729, 2018.
Artigo em Japonês | MEDLINE | ID: mdl-30587679

RESUMO

Objective The purpose of this study was to examine the relationship between intra- and inter-generational exchange and mental health among young adults aged 25-49 years and older adults aged 65-84 years.Methods In 2016, a community-based, cross-sectional survey was conducted. A total of 3,334 young adults (valid response rate: 24.6%), and 3,116 older adults (valid response rate: 46.0%) completed the survey and were included in the analysis. Their mental health was evaluated using the World Health Organization-Five Well-Being Index (WHO-5), and those who scored under 13 or scored less than one on any item were considered to have poor mental health. To evaluate the intra- or inter-generational exchange, participants were asked about their frequency of interaction with people aged 20-49 years or aged ≥70, excluding family and co-workers. Young adults who interacted with people aged 20-49 years or older adults who interacted with people ≥70 were classified as "having intra-generational exchange," while young adults who interacted with people ≥70 years or older adults who interacted with people aged 20-49 years were classified as "having intergenerational exchange." Therefore, individuals who interacted with both generations were classified as "having multi-generational exchange," and those who did not interact with any generation were categorized as "no exchange." We conducted a logistic regression analysis that included mental health as a dependent variable, intra- and inter-generational exchange as independent variables, and gender, age, educational attainment, marital status, living situation, subjective economic status, social participation, employment, self-rated health, and Instrumental Activity of Daily Living as covariates.Results Of the 3,334 young adults, 61.5% were mentally healthy, 51.3% had intra-generational exchange, 21.9% had inter-generational exchange, 16.5% had multi-generational exchange, and 42.7% did not have any exchange. Of the 3,116 older adults, 65.8% were mentally healthy, 67.9% had intra-generational exchange, 34.3% had inter-generational exchange, 29.9% had multi-generational exchange, and 21.1% did not have any exchange. A logistic regression analysis revealed that "having intra-generational exchange" and "having intergenerational exchange" were significantly related to better mental health in both young adults (intra-generational; Odds ratios (OR) 1.19, 95% confidence intervals (CI) 1.10-1.30: inter-generational; OR 1.13, 95% CI 1.03-1.25) and older adults (intra-generational; OR 1.15, 95% CI 1.02-1.29: inter-generational; OR 1.46, 95% CI 1.30-1.65). Therefore, "having multi-generational exchange" was more strongly related to better mental health compared with "only having intra-generational exchange."Conclusion Among young and older adults, intra- and inter-generational exchange were related to better mental health, and multi-generational exchange showed the strongest relationship with better mental health.


Assuntos
Relação entre Gerações , Saúde Mental , Atividades Cotidianas , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Escolaridade , Emprego , Feminino , Nível de Saúde , Humanos , Modelos Logísticos , Masculino , Estado Civil , Pessoa de Meia-Idade , Participação Social , Fatores Socioeconômicos , Inquéritos e Questionários
9.
Nihon Koshu Eisei Zasshi ; 65(7): 321-333, 2018.
Artigo em Japonês | MEDLINE | ID: mdl-30068818

RESUMO

Objectives Using the Community Child-Rearing Support Scale (CCRSS), which was developed for older adults, we examined 1) the reliability and validity of the scale for multiple generations, as well as the generational differences in the 2) degree and content of supportive behaviors for child rearing and 3) correlates of the behavior, in conjunction with gender differences.Methods A mail survey was conducted with residents aged 25-84 years who were randomly selected from two cities in Tokyo and the surrounding areas, and responses were obtained from 8918 residents (response rate: 33%). The respondents were grouped as follows: old-aged (65-84 years), middle-aged (50-64 years), and young-aged (25-49 years). We performed the following analyses by age group and gender: 1) Cronbach's reliability coefficient and a confirmatory factor analysis of the CCRSS, 2) analysis of variance of the total CCRSS scores and scores of the three subscales ("children's security and sound growth," "instrumental support to parents," and "emotional support to parents"), and 3) a multiple regression analysis of the total scores in which various individual characteristics were introduced as explanatory variables.Results The reliability coefficient was over 0.85 for each age group, and the factor analysis showed good model fitness. Compared to the middle- and young-aged groups, the old-aged group was more likely to provide support for "children's security and sound growth," and equally (for women) or more likely (for men) to provide "emotional support to parents," thereby resulting in the highest total score among the three generations. The mean score of "instrumental support to parents," such as taking care of a child, was the highest for young women, although the score was low overall. Having a child or grandchild under 13 years old and stronger generativity were positively associated with child-rearing support for all age groups; however, the degree of associations varied across the groups. While having a child was strongly associated with support among the young-aged group, the association between support and generativity was stronger for older groups. Moreover, participation in neighborhood associations or volunteer groups and high school or lower education were associated with more support among all age groups, whereas living in rental apartments was associated with less support among the young-aged group.Conclusion Our findings suggest that the CCRSS can be used for multiple generations and that old people play an important role in child rearing in the community. We found both differences and similarities between generations with respect to the correlates of child-rearing support.


Assuntos
Educação Infantil/psicologia , Participação da Comunidade/estatística & dados numéricos , Relação entre Gerações , Pais/psicologia , Apoio Social , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Emoções , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Fatores Sexuais
10.
Glia ; 65(9): 1491-1503, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28581152

RESUMO

Neurosteroid dehydroepiandrosterone (DHEA) has been reported to exert a potent neuroprotective effect against glutamate-induced excitotoxicity. However, the underlying mechanism remains to be elucidated. One of the possible mechanisms may be an involvement of astrocytic glutamate transporter subtype-1 (GLT-1) that can quickly clear spilled glutamate at the synapse to prevent excitotoxicity. To examine the effect of DHEA on GLT-1 activity, we measured synaptically induced glial depolarization (SIGD) in the dentate gyrus (DG) of adult rats by applying an optical recording technique to the hippocampal slices stained with voltage-sensitive dye RH155. Bath-application of DHEA for 10 min dose-dependently increased SIGD without changing presynaptic glutamate releases, which was sensitive to the GLT-1 blocker DHK. Patch-clamp recordings in astrocytes showed that an application of 50 µM DHEA increased glutamate-evoked inward currents (Iglu) by approximately 1.5-fold, which was dependent on the GLT-1 activity. In addition, the level of biotinylated GLT-1 protein in the surface of astrocytes was significantly elevated by DHEA. The DHEA-increased SIGD, Iglu, and GLT-1 translocation to the cell surface were blocked by the σ1 R antagonist NE100 and mimicked by the σ1 R agonist PRE084. DHEA elevated the phosphorylation level of PKC in a σ1 R-dependent manner. Furthermore, the PKC inhibitor chelerythrine could prevent the DHEA-increased SIGD, Iglu, and GLT-1 translocation. Collectively, present results suggest that DHEA enhances the activity and translocation to cell surface of astrocytic GLT-1 mainly via σ1 R-mediated PKC cascade.


Assuntos
Astrócitos/metabolismo , Desidroepiandrosterona/metabolismo , Giro Denteado/metabolismo , Transportador 2 de Aminoácido Excitatório/metabolismo , Proteína Quinase C/metabolismo , Receptores sigma/metabolismo , Animais , Astrócitos/efeitos dos fármacos , Fármacos do Sistema Nervoso Central/administração & dosagem , Proteínas Quinases Dependentes de AMP Cíclico/antagonistas & inibidores , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Desidroepiandrosterona/administração & dosagem , Giro Denteado/efeitos dos fármacos , Ácido Glutâmico/efeitos dos fármacos , Ácido Glutâmico/metabolismo , Receptores de Inositol 1,4,5-Trifosfato/metabolismo , Masculino , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Fosforilação/efeitos dos fármacos , Fosforilação/fisiologia , Proteína Quinase C/antagonistas & inibidores , Transporte Proteico/efeitos dos fármacos , Transporte Proteico/fisiologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Wistar , Receptores sigma/agonistas , Receptores sigma/antagonistas & inibidores , Técnicas de Cultura de Tecidos
11.
Opt Express ; 25(11): 12069-12080, 2017 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-28786565

RESUMO

A high visibility Hong-Ou-Mandel (HOM) interference between two independently prepared photons plays an important role in various photonic quantum information processing. In a standard HOM experiment using photons generated by pulse-pumped spontaneous parametric down conversion (SPDC), larger detection time windows than the coherence time of photons have been employed for measuring the HOM visibility and/or drawing the HOM dip. If large amounts of stray photons continuously exist within the detection time windows, employing small detection time windows is favorable for reducing the effect of background noises. Especially, such a setup is helpful for the HOM experiment using continuous wave (cw)-pumped SPDC and the time-resolved coincidence measurement. Here we argue that the method for determining the HOM visibility used in the previous cw experiments tends to suffer from distortion arising from biased contribution of the background noises. We then present a new method with unbiased treatment of the cw backgrounds. By using this method, we experimentally demonstrate a high visibility HOM interference of two heralded telecom photons independently generated by SPDC with employing cw pump light. An observed HOM visibility is 0.87 ± 0.04, which is as high as those observed by using pulse-pumped SPDC photons.

12.
Anal Bioanal Chem ; 409(4): 961-969, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27838750

RESUMO

Investigation of the positional heterogeneity of messenger RNA (mRNA) expression in tissues requires a technology that facilitates analysis of mRNA expression in the selected single cells. We developed a mille-feuille probe (MP) that allows the lamination of the aqueous and organic phases in a nanopipette under voltage control. The MP was used for continuous collection of different nucleic acid samples and sequential evaluation of gene expression with mRNA barcoding tags. First, we found that the aqueous phases could be laminated into five individual layers and separated by the plugs of the organic phases in a nanopipette when the salt (THATPBCl) concentration in the organic phase was 100 mM. Second, the aspiration rate of the MP was stabilized and the velocity of the aqueous phase in the MP was lowered at higher THATPBCl concentrations in the organic phase. This was because the force during ingression of the aqueous phase into the organic - phase-filled nanopipette induced an electro-osmotic flow between the inside wall of the nanopipette and THATPBCl in the organic phase. Third, inclusion of mRNA barcoding tags in the MP facilitated complementary DNA construction and sequential analysis of gene expression. This technique has potential to be applicable to RNA sequencing from different cell samples across the life sciences. Graphical abstract We developed a mille-feuille probe (MP) that allows the lamination of the aqueous and organic phases in a nanopipette under voltage control.


Assuntos
DNA Complementar/análise , Sondas Moleculares , RNA Mensageiro/análise , Sequência de Bases , Humanos , Limite de Detecção , Células MCF-7 , Reação em Cadeia da Polimerase/métodos
13.
J Neurosci ; 34(45): 14995-5008, 2014 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-25378165

RESUMO

Synaptic plasticity in hippocampal neurons has been thought to represent a variety of memories. Although accumulating evidence indicates a crucial role of BDNF/TrkB/Akt signaling in the synaptic plasticity of the hippocampus, the mechanism by which Akt, a serine/threonine kinase, controls activity-dependent neuronal plasticity remains unclear. Girdin (also known as APE, GIV, and HkRP1), an actin-binding protein involved both in the remodeling of the actin cytoskeleton and in cell migration, has been identified as a substrate of Akt. Previous studies have demonstrated that deficit of neuronal migration in the hippocampus of Girdin-deficient (Girdin(-/-)) mice is independent on serine phosphorylation of Girdin at S1416 (Girdin S1416) by Akt. In the present study, we focused on the role of Girdin S1416 phosphorylation in BDNF/TrkB/Akt signaling associated with synaptic plasticity. We found that Girdin in the hippocampus was phosphorylated at S1416 in an activity-dependent manner. Phosphorylation-deficient knock-in mice (Girdin(SA/SA) mice), in which S1416 is replaced with alanine, exhibited shrinkage of spines, deficit of hippocampal long-term potentiation, and memory impairment. These phenotypes of Girdin(SA/SA) mice resembled those of Girdin(+/-) mice, which have 50% loss of Girdin expression. Furthermore, Girdin interacted with Src kinase and NR2B subunit of NMDA receptor, leading to phosphorylation of the NR2B subunit and NMDA receptor activation. Our findings suggest that Girdin has two different functions in the hippocampus: Akt-independent neuronal migration and Akt-dependent NR2B phosphorylation through the interaction with Src, which is associated with synaptic plasticity in the hippocampus underlying memory formation.


Assuntos
Potenciação de Longa Duração , Memória , Proteínas dos Microfilamentos/metabolismo , Neurônios/metabolismo , Processamento de Proteína Pós-Traducional , Receptores de N-Metil-D-Aspartato/metabolismo , Transdução de Sinais , Proteínas de Transporte Vesicular/metabolismo , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Células Cultivadas , Espinhas Dendríticas/metabolismo , Hipocampo/citologia , Hipocampo/metabolismo , Hipocampo/fisiologia , Camundongos , Proteínas dos Microfilamentos/genética , Neurônios/citologia , Neurônios/fisiologia , Fosforilação , Ligação Proteica , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor trkB/metabolismo , Proteínas de Transporte Vesicular/genética , Quinases da Família src/metabolismo
14.
Transl Stroke Res ; 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39172309

RESUMO

Stroke is a leading cause of death and disability worldwide. Tissue plasminogen activator (tPA) is currently the most effective medicine for stroke; however, it has a narrow therapeutic time window (4.5 h after symptom onset). We demonstrated that nestorone, a progesterone (P4) receptor agonist, exerted neuroprotective effects against transient focal cerebral ischemia 6 h post-ischemic administration in adult male rats. This study examines its effects on permanent focal cerebral ischemia in adult and aged male rats, which are better models for evaluating treatment outcomes in typical stroke patients. Adult (6-month-old) or aged (18-month-old) male rats subjected to permanent middle cerebral artery occlusion (pMCAO) were continuously administered nestorone (10µg/day) or its vehicle (30% hydroxypropyl-ß-cyclodextrin) for 7 days via an osmotic pump subcutaneously implanted, starting at 18 h post-pMCAO. Nestorone-treated adult male rats showed marked improvements in behavioral outcomes in the adhesive removal and rotarod tests and a significant reduction in infarct size compared to vehicle-treated rats 9 and 30 days post-pMCAO. The same administration of nestorone resulted in apparently comparable neuroprotective effects in aged male rats. The inflammatory mediator NF-κB/p65 was increased in Iba-1 positive cells 24 h post-pMCAO, but was significantly suppressed by subcutaneous injection of nestorone. These results suggested that nestorone exerts long-term neuroprotective effects against permanent focal cerebral ischemia in adult and aged male rats. Nestorone is thus a promising agent for post-stroke treatment owing to its wide age-independent therapeutic time window (18 h after symptom onset), which is longer than that of tPA therapy.

15.
Hum Mol Genet ; 20(23): 4666-83, 2011 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-21903668

RESUMO

Disrupted-In-Schizophrenia 1 (DISC1) is a promising candidate gene for susceptibility to psychiatric disorders, including schizophrenia. DISC1 appears to be involved in neurogenesis, neuronal migration, axon/dendrite formation and synapse formation; during these processes, DISC1 acts as a scaffold protein by interacting with various partners. However, the lack of Disc1 knockout mice and a well-characterized antibody to DISC1 has made it difficult to determine the exact role of DISC1 in vivo. In this study, we generated mice lacking exons 2 and 3 of the Disc1 gene and prepared specific antibodies to the N- and C-termini of DISC1. The Disc1 mutant mice are viable and fertile, and no gross phenotypes, such as disorganization of the brain's cytoarchitecture, were observed. Western blot analysis revealed that the DISC1-specific antibodies recognize a protein with an apparent molecular mass of ~100 kDa in brain extracts from wild-type mice but not in brain extracts from DISC1 mutant mice. Immunochemical studies demonstrated that DISC1 is mainly localized to the vicinity of the Golgi apparatus in hippocampal neurons and astrocytes. A deficiency of full-length Disc1 induced a threshold shift in the induction of long-term potentiation in the dentate gyrus. The Disc1 mutant mice displayed abnormal emotional behavior as assessed by the elevated plus-maze and cliff-avoidance tests, thereby suggesting that a deficiency of full-length DISC1 may result in lower anxiety and/or higher impulsivity. Based on these results, we suggest that full-length Disc1-deficient mice and DISC1-specific antibodies are powerful tools for dissecting the pathophysiological functions of DISC1.


Assuntos
Comportamento Animal , Éxons/genética , Marcação de Genes , Proteínas do Tecido Nervoso/genética , Envelhecimento/efeitos dos fármacos , Envelhecimento/patologia , Aminas/metabolismo , Animais , Anticorpos/imunologia , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Astrócitos/patologia , Comportamento Animal/efeitos dos fármacos , Clozapina/farmacologia , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Hipocampo/crescimento & desenvolvimento , Hipocampo/metabolismo , Hipocampo/patologia , Hipocampo/ultraestrutura , Imuno-Histoquímica , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos , Proteínas do Tecido Nervoso/imunologia , Plasticidade Neuronal/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Fenótipo , Transmissão Sináptica/efeitos dos fármacos , Fatores de Tempo
16.
J Plant Res ; 126(2): 243-50, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22878456

RESUMO

Totipotency is the ability of a cell to regenerate the entire organism, even after previous differentiation as a specific cell. When totipotency is coupled with active cell division, it was presumed that cell division is essential for this expression. Here, using the stress-induction system of somatic embryos in carrots, we show that cell division is not essential for the expression of totipotency in somatic/embryonic conversion. Morphological and histochemical analyses showed that the cell did not divide during embryo induction. Inhibitors of cell division did not affect the rate of somatic embryo formation. Our results indicate that the newly acquired trait of differentiation appears without cell division, but does not arise with cell division as a newborn cell.


Assuntos
Diferenciação Celular/fisiologia , Divisão Celular/efeitos dos fármacos , Daucus carota/citologia , Daucus carota/fisiologia , Técnicas de Embriogênese Somática de Plantas , Afidicolina/farmacologia , Benzamidas/farmacologia , Inibidores Enzimáticos/farmacologia , Hibridização In Situ , Estresse Fisiológico , Células-Tronco Totipotentes/citologia
17.
Hippocampus ; 22(4): 707-22, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21484933

RESUMO

The neurosteroid dehydroepiandrosterone-sulfate (DHEAS) is a positive modulator of synaptic transmission in mammalian brains; however, the underlying molecular mechanisms are not fully understood. This report describes the acute effects of DHEAS on the synaptic transmission in the hippocampal dentate gyrus of rat brain slices. The application of DHEAS for 10 min augmented the optically recorded EPSP (op-EPSP) in a dose dependent manner. The effect became visible at 1 nM and saturated at 100 nM. We focused on the effect of DHEAS at 100 nM, where the op-EPSP amplitude was increased by 30%, and gradually decreased to the basal level in 30 min after wash out of the drug (short-term potentiation by DHEAS; STP(DHEAS)). DHEAS did not alter the presynaptic properties including the presynaptic fiber volley (PSFV) and paired pulse facilitation (PPF), thus indicating that the acute DHEAS effect is of postsynaptic origin. The involvement of putative DHEAS targets, GABA(A), NMDA, and σ1 receptors in STP(DHEAS) was also investigated; however, antagonists to these receptors only partially inhibited the acute effect of DHEAS. By contrast, STP(DHEAS) was totally inhibited by either the metabotropic glutamate receptor 5 (mGluR5) antagonist MPEP (10 µM) or the ryanodine receptor (RyR) inhibitors (ryanodine and ruthenium red), but not by the mGluR1 antagonist LY367385 and the IP3R antagonist 2-APB, suggesting that STP(DHEAS) is mediated by an mGluR5-RyR cascade in postsynaptic neurons. Consistent with this finding, the selective agonist for mGluR5 CHPG nearly perfectly mimicked the DHEAS effect. This is the first demonstration of mGluR involvement in the DHEAS action in regard to hippocampal synaptic transmission.


Assuntos
Sulfato de Desidroepiandrosterona/farmacologia , Hipocampo/efeitos dos fármacos , Hipocampo/fisiologia , Receptores de Glutamato Metabotrópico/agonistas , Transmissão Sináptica/efeitos dos fármacos , Animais , Sinalização do Cálcio/efeitos dos fármacos , Sinalização do Cálcio/fisiologia , Sulfato de Desidroepiandrosterona/administração & dosagem , Giro Denteado/efeitos dos fármacos , Giro Denteado/fisiologia , Estimulação Elétrica , Agonistas de Aminoácidos Excitatórios/administração & dosagem , Agonistas de Aminoácidos Excitatórios/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/fisiologia , Glicina/análogos & derivados , Glicina/farmacologia , Potenciação de Longa Duração/efeitos dos fármacos , Potenciação de Longa Duração/fisiologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/fisiologia , Masculino , Fenilacetatos/farmacologia , Ratos , Ratos Wistar , Receptor de Glutamato Metabotrópico 5 , Receptores de Glutamato Metabotrópico/antagonistas & inibidores , Receptores de Glutamato Metabotrópico/fisiologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Transmissão Sináptica/fisiologia
18.
Clin Case Rep ; 10(3): e05416, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35261771

RESUMO

Here, we report a case of traumatic pulmonary pseudocysts (TPPs) coinciding with vertebral fracture. Traumatic pulmonary pseudocysts (TPPs) are rare complications of blunt chest trauma. These clinical images of CT, presenting here, seemed to be valuable because they show the process of pseudocyst formation.

19.
Artigo em Inglês | MEDLINE | ID: mdl-35206406

RESUMO

This study aims to identify the independent influence of face-to-face contact (FFC) and non-face-to-face contact (NFFC) on the subsequent decline in self-rated health and mental health status by age. A total of 12,000 participants were randomly selected among residents in the study area, and 1751 of them responded to both the 2016 and 2018 mail surveys. The participants were subsequently classified into three age groups (25-49: Young adults; 50-64: Mid-aged adults; and 65-84: Older adults). Social contact was assessed by computing the frequencies of FFC and NFFC. Multiple logistic regression analysis showed the risk of social contact on the decline in self-rated health and World Health Organization-Five Well-Being Index. Both FFC and NFFC were significantly associated with maintaining mental health; however, the impacts of FFC on mental health were more significant than that of NFFC among older adults and young adults. Compared with the no contact group, FFC was significantly associated with maintaining self-rated health in mid-aged adults. The influence of FFC and NFFC on health differed by age group.


Assuntos
Nível de Saúde , Relações Interpessoais , Saúde Mental , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Japão/epidemiologia , Pessoa de Meia-Idade , Estudos Prospectivos , Inquéritos e Questionários
20.
J Exp Med ; 219(4)2022 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-35297954

RESUMO

New neurons, continuously added in the adult olfactory bulb (OB) and hippocampus, are involved in information processing in neural circuits. Here, we show that synaptic pruning of adult-born neurons by microglia depends on phosphatidylserine (PS), whose exposure on dendritic spines is inversely correlated with their input activity. To study the role of PS in spine pruning by microglia in vivo, we developed an inducible transgenic mouse line, in which the exposed PS is masked by a dominant-negative form of milk fat globule-EGF-factor 8 (MFG-E8), MFG-E8D89E. In this transgenic mouse, the spine pruning of adult-born neurons by microglia is impaired in the OB and hippocampus. Furthermore, the electrophysiological properties of these adult-born neurons are altered in MFG-E8D89E mice. These data suggest that PS is involved in the microglial spine pruning and the functional maturation of adult-born neurons. The MFG-E8D89E-based genetic approach shown in this study has broad applications for understanding the biology of PS-mediated phagocytosis in vivo.


Assuntos
Microglia , Fosfatidilserinas , Animais , Antígenos de Superfície/genética , Camundongos , Camundongos Transgênicos , Plasticidade Neuronal , Neurônios
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